This phase I/II trial is studying the side effects of erlotinib and to see how well it works in treating patients with metastatic or unresectable non-small cell lung cancer, ovarian cancer, or squamous cell carcinoma (cancer) of the head and neck. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth
PRIMARY OBJECTIVES: I. To determine if a significant correlation exists between the length of the CA dinucleotide repeat polymorphism in the EGFR gene and observed toxicity in patients treated with OSI-774. SECONDARY OBJECTIVES: I. To study the pharmacodynamic effects of OSI-774 on EGFR activity and MAP kinase signaling using skin as a surrogate tissue. II. To determine if interindividual variation of OSI-774 pharmacokinetics is related to a previously described CYP3A5 genetic polymorphism. III. To evaluate whether toxicity or inhibition of EGFR phosphorylation correlates with OSI-774 AUC in patients treated with OSI-774. IV. To describe the observed anti-tumor response and toxicities in patients with advanced solid tumors treated with single agent fixed dose of OSI-774. OUTLINE: This is a multicenter study. Patients are stratified according to length of CA dinucleotide repeat polymorphism (short vs medium vs long). Patients receive oral erlotinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
80
Given PO
Correlative studies
Correlative studies
Correlative studies
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Rate of diarrhea and skin rash across the short, medium, and long genotype frequencies of the CA polymorphism
Compared using Armitage's test for a trend in proportions. In the event that the relationship between toxicity and length of the polymorphism is not monotone, a two degree-of-freedom chisquare test will be used in place of the trend test. The number of CA repeats treated as a continuous variable by averaging the number of repeats on each chromosome. Logistic regression analysis will then be performed to model the probability of toxicity as a function of the average length.
Time frame: Baseline
Rate of diarrhea and skin rash across the short, medium, and long genotype frequencies of the CA polymorphism
Compared using Armitage's test for a trend in proportions. In the event that the relationship between toxicity and length of the polymorphism is not monotone, a two degree-of-freedom chisquare test will be used in place of the trend test. The number of CA repeats treated as a continuous variable by averaging the number of repeats on each chromosome. Logistic regression analysis will then be performed to model the probability of toxicity as a function of the average length.
Time frame: Week 6
Pharmacodynamic effects of erlotinib hydrochloride on EGFR activity and MAP kinase signaling
Time frame: Week 1
Observed anti-tumor responses
Number of patients with complete or partial tumor responses and will be tabulated; 95% confidence intervals will be generated.
Time frame: Up to 4 years
All observed toxicities
The frequency of adverse events will be tabulated; 95% confidence intervals will be generated.
Time frame: Up to 4 years
Erlotinib hydrochloride AUC
Compared with incidence of toxicity in patients with at least one 3A5\*1 allele to those with no 3A5\*1 allele using two-sample t and chi square tests, respectively. The relationship between toxicity and AUC evaluated by fitting ordinal (proportional odds) logistic regression models in which the grade of toxicity is the dependent variable and AUC is the independent or predictor variable. If the proportional odds model does not provide a good fit to the data then the toxicity grade will be dichotomized and analyzed using and analyzed using ordinary logistic regression.
Time frame: Baseline, 0.5, 1, 2, 4, and 6 h after initiation, and pre-treatment days 15 and 29
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